Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China.
Department of Pediatrics, Peking University People's Hospital, Beijing, 100034, China.
Orphanet J Rare Dis. 2022 Sep 2;17(1):330. doi: 10.1186/s13023-022-02471-x.
cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty.
This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, L-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies.
Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, L-carnitine, and betaine appears to be beneficial.
cblC 缺乏症是中国最常见的甲基丙二酸血症类型。迟发性患者表现出各种非特异性症状，通常被误诊。本研究旨在探讨迟发性 cblC 缺乏症患者的临床特征，并探讨青春期前后的诊断和治疗策略。
本研究纳入了 2002 年至 2021 年 9 月期间在我院就诊的 56 例迟发性 cblC 缺乏症患者（男 35 例，女 21 例）。通过代谢和基因检测确诊。检查了临床和生化特征、疾病诱因、结局和相关的遗传变异。发病年龄为 10 至 20 岁（中位年龄 12 岁）。15 例（26.8%）在感染或运动训练后出现症状。此外，46 例（82.1%）有神经精神疾病；11 例（19.6%）心血管疾病；6 例（10.7%）肺动脉高压。6 例（10.7%）有肾脏损害。56 例患者的 MMACHC 基因有 21 种变异。在 112 个等位基因中，检测到前 5 种常见变异为 c.482G > A（36.6%）、c.609G > A（16.1%）、c.658_660delAAG（9.8%）、c.80A > G（8.0%）和 c.567dupT（6.3%）。39 例患者携带 c.482G > A 变异。在以痉挛性截瘫为主要表现的 13 例患者中，11 例携带 c.482G > A 变异。6 例表现为精神障碍和痉挛性截瘫的患者为复合杂合性 c.482G > A 和其他变异。所有患者在接受钴胺素、左旋肉碱和甜菜碱代谢治疗后均有改善，30 名学龄期患者返回学校。2 名女性患者结婚并生育健康婴儿。
迟发性 cblC 缺乏症患者表现出广泛的神经精神症状和其他表现，包括多器官损伤。因此，cb1C 缺乏症很容易被误诊为其他疾病。代谢和基因研究对准确诊断很重要，用钴胺素、左旋肉碱和甜菜碱进行代谢治疗似乎是有益的。
